The godfather himself: Robert Weinberg visits the Moores Cancer Center

24 January 2013

Yesterday I had the pleasure of attending a talk by Robert Weinberg, perhaps one of the most influential scientists to ever tackle cancer. Weinberg pioneered research on oncogenes and tumor suppressor genes, and his 2000 review paper The Hallmarks of Cancer carries the distinction as the most cited paper in Cell and even has its own wikipedia page.

These days Weinberg is still at it, and his group at MIT is no less prolific in their publishing. His lab today works on two (somewhat converging) areas of cancer biology that are both highly contentious and controversial: cancer stem cells (CSC) and “epithelial to mesenchymal transition” (EMT).

As I’ve stressed time and time again in my blog: the vast majority of cancer mortality and debilitating effects of the disease are caused by metastasis, or the spread of cancer to vital organs. The leading theory on HOW cancer cells are able to spread and seed distant organs is EMT. The theory essentially proposes that cancer cells in a primary (epithelial) tumor are able to de-differentiate into a (mesenchymal) state, allowing them to change shape and turn from cellular bricks to contortionists, enabling them to weave their way through tissues to blood vessels, and after a ride through the blood stream, exit by slipping between endothelial cells lining capillaries, then re-differentiating from contortionists (mesenchymal) to cellular bricks (epithelial) again. See image.

The evidence for this process occurring in (human engineered) mouse models of cancer is pretty good. However, this theory has come under fire due to the utter lack of histological evidence from hundreds of thousands of human patient biopsies every year. Granted, EMT is theorized to be a transient event, and not all pathologists are really looking for evidence of EMT all the time; they’re usually looking at other clues in the tumor for how to best treat an individual patient. However, in science the onus is to prove that something exists, not that something does not exist. Does EMT really occur in humans? Would this mechanism be of use to cancer therapeutic strategies? At the time of this writing, these questions remain open-ended.

My problem with EMT is that the definition changes from researcher to researcher, and can at times even be contradicting. It’s become a scientific buzzword often used to make new research appear concise and consistent when in fact valuable nuances might be glossed over in the process. Granted, theories can change over time with new data and observations, and it is possible that not everyone is on the same page. I was really hoping that Weinberg would have provided a concise definition of EMT in his talk. Instead, problems with the phenomena were pseudo-discussed in terms of “partial EMT” or “limited EMT.”

I will discuss the evolution of the cancer stem cell hypothesis (and how this is affecting therapeutic approach and drug investment) when I have more time, but for the moment I must step away from the keyboard and attend to my cell cultures!

Ryon